Nicolaou, Sarlah and Shaw. ACIEE, 2007, Early View. DOI: 10.1002/anie.200701552.
I wasn’t planning on putting this synthesis up today; in fact, I’ve got a tasty number from Steve Ley to put up. However, one glance at the palladium cascade in this paper left me with my jaw on the floor, and I’d started transcribing the structures before I knew it! So, a quick look at the biological activity would be in order: selective inhibitory activity against HIV replication in H9 lymphocytes (EC50=0.798 Î¼g) with a TI of about 31.3, …

Macherla, Manam, McArthur and Potts. Org, 2007, ASAP. DOI: 10.1021/ol0706051 .
This target has certainly seen it’s share of interest, and you certainly know it’s an interesting target if industry decide to make it! Indeed, this paper is by some folks at Nereus Pharmaceuticals, San Diego, who were clearly interested in its 20S proteasome busting activity (read inhibition). Although there have been several syntheses of Salinosporamide A, the group state that they needed a route suitable for analogue generation – apparently that beta-lactone is a bit of …

Many of you will have noticed that I have a forum on this site; if you haven’t, it’s accessible from the link above. However, I’ve a had a bit of trouble with spammers, so I’d closed new regisrations for quite a while. Since then, though, I’ve opened up registration again, and hope things clean up a little.
So if your got something on your mind, chemistry or not, then head on over!

D. Kim, Park, B. Kim, H. Kim, and D. Kim. ACIEE, 2006, Early View. DOI: 10.1002/anie.200700854.
Again with the medium rings! And what a target – I’m still surprised to see that bromo-allene in a natural product, but nature is known for her surprises… This time, however, the focus isn’t really on the eight-ring, but on the six, with a slightly tricky bromide to introduce.
The starting point for the synthesis was a Grignard addition into an aldehyde, setting up the stereochemistry from a chiral aldehyde. Formation of the …

Takahashi, Doi, Iijima and Takasaki. JOC, 2007, ASAP. DOI: 10.1021/jo062546v.
At first, I loved the look of this synthesis; take one really simple acyclic precursor, dump in a little of everyone’s (or at least my) favourite palladium catalyst, and hey-presto – instant 5,5-spiro fused ring system. However, after that reaction, things go off-the-rails a little…
The substrate, as I said, was made very quickly, doing a double Tsuji-Trost allylic alkylation with the bis(phenylsulfonyl)methane on two allyl halides (okay, one is an allyl acetate…). They were then set to cyclise, using the same …

Nicolaou. ACIEE, 2006, Early View. DOI: 10.1002/anie.200604656.
Nope, it’s not done yet (slackers…), but there’s a very interesting KCN penned piece in Angewandte this week as an essay on the structure of Maitotoxin. It’s certainly been an intimidating challenge for the synthetic community for sometime, but with a molecular weight of 3422 g-1mol, LD50 of 50ng (yes, nanograms… I read a paper that states “a gram of maitotoxin can kill
approximately half a billion mice”), and nearly 100 stereocentres, it’s going to take some doing. Interestingly, there may be a flaw in …

Feng, Tian, Yuan, Mu and He. Org. Lett., 2007, 9, 2019. DOI: 10.1021/ol070597o.
Bear with me on this one – I guess you’ve seen this target before. I was shown this paper by a few of the chaps in our group, and was just astounded with the transformation, and even more by the mechanism.

Awesome! But the mechanism contains some rather worrying steps. I’ve capture the entire thing directly from the supp. info., cause even I can’t be bothered redrawing that:

(The supp. info., BTW, is here.)
I’m particularly concerned by the Fe-mediated …

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About Tot. Syn.

It's all about stirring pots and hoping for shiny white crystals. Read-on to see some of the best modern organic chemistry, and comments from the folks at the bench.